Delayed rehabilitation with task-specific therapies improves forelimb function after a cervical spinal cord injury

Dai, Haining; MacArthur, Linda; McAtee, Marietta; Hockenbury, Nicole; Das, Paramita; Bregman, Barbara S.

doi:10.3233/rnn-2011-0583

Cited by 16 publications

(10 citation statements)

References 64 publications

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“…The mean duty factor increased in both hindlimbs (not significantly in the right, p=0.152), but significantly decreased in the right forelimb while significantly increasing in the left. These results are consistent with previous C4/5 right overhemisection injuries performed by our laboratory (Bregman et al, 1993–Lynskey et al, 2006,Dai et al, 2009–Dai et al, 2011). …”

Section: Resultssupporting

confidence: 93%

Quantifying changes following spinal cord injury with velocity dependent locomotor measures

Neckel

Dai

Bregman

2013

Journal of Neuroscience Methods

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Many locomotor measures commonly used to assess functional deficits following neurological injury are velocity dependent. This makes the comparison of faster pre-injury walking to slower post-injury walking a challenging process. In lieu of calculating mean values at specific velocities, we have employed the use of nonlinear regression techniques to quantify locomotor measures across all velocities. This enables us to assess more accurately the locomotor recovery of rats after a cervical spinal cord injury. For example, while the mean stride length of the hindlimbs decreased following injury, regression analysis revealed that the change was due to the reduction in walking speed and not a functional deficit. A significant difference in the percent of the right forelimb step cycle that was spent in stance phase, or duty factor, was found across all velocities, however this deficit spontaneously recovered after 6 weeks. Conversely, no differences were initially found in hindlimb stride length, but abnormal compensatory techniques were found to have developed 3 weeks after injury.

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Section: Resultssupporting

confidence: 93%

Quantifying changes following spinal cord injury with velocity dependent locomotor measures

Neckel

Dai

Bregman

2013

Journal of Neuroscience Methods

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“…The following variables within the Other Statistics category are routinely used as stand‐alone measures and/or as criteria for run compliance. BOS reflects stance width for the front or hind paws, and is commonly studied in the context of spinal cord injury (Dai et al ; Petrosyan et al ; Streijger et al ). BOS for the hind paws ↑ slightly WIS, while the BOS for the front paws ↓, suggesting a narrowing of front stance and a widening of hind stance WIS (Fig.…”

Section: Resultsmentioning

confidence: 99%

The Need for Speed in Rodent Locomotion Analyses

Batka

Brown

McMillan

et al. 2014

The Anatomical Record

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Locomotion analysis is now widely used across many animal species to understand the motor defects in disease, functional recovery following neural injury, and the effectiveness of various treatments. More recently, rodent locomotion analysis has become an increasingly popular method in a diverse range of research. Speed is an inseparable aspect of locomotion that is still not fully understood, and its effects are often not properly incorporated while analyzing data. In this hybrid manuscript, we accomplish three things: (1) review the interaction between speed and locomotion variables in rodent studies, (2) comprehensively analyze the relationship between speed and 162 locomotion variables in a group of 16 wild-type mice using the CatWalk gait analysis system, and (3) develop and test a statistical method in which locomotion variables are analyzed and reported in the context of speed. Notable results include the following: (1) over 90% of variables, reported by CatWalk, were dependent on speed with an average R2 value of 0.624, (2) most variables were related to speed in a nonlinear manner, (3) current methods of controlling for speed are insufficient, and (4) the linear mixed model is an appropriate and effective statistical method for locomotion analyses that is inclusive of speed-dependent relationships. Given the pervasive dependency of locomotion variables on speed, we maintain that valid conclusions from locomotion analyses cannot be made unless they are analyzed and reported within the context of speed.

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“…We therefore changed the design of the treatment protocol in order to accommodate the requirements that anti-Nogo-A be delivered within 2 weeks of injury (Gonzenbach et al, 2010(Gonzenbach et al, , 2012 and that rehabilitation be initiated after anti-Nogo-A treatment has finished. The timing of onset of ChABC treatment is not critical, and may be extended up to 1 year after injury Alilain & Silver, 2012), and delayed rehabilitation alone has also been shown to improve forelimb function after SCI (Dai et al, 2011). Moreover, rehabilitation at the same time as ChABC treatment has been successful Wang et al, 2011;Alilain & Silver, 2012).…”

Section: Discussionmentioning

confidence: 99%

Combination treatment with anti‐Nogo‐A and chondroitinase ABC is more effective than single treatments at enhancing functional recovery after spinal cord injury

Zhao

Andrews

Wang

et al. 2013

Eur J of Neuroscience

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Anti-Nogo-A antibody and chondroitinase ABC (ChABC) enzyme are two promising treatments that promote functional recovery after spinal cord injury (SCI). Treatment with them has encouraged axon regeneration, sprouting and functional recovery in a variety of spinal cord and central nervous system injury models. The two compounds work, in part, through different mechanisms, so it is possible that their effects will be additive. In this study, we used a rat cervical partial SCI model to explore the effectiveness of a combination of anti-Nogo-A, ChABC, and rehabilitation. We found that spontaneous recovery of forelimb functions reflects the extent of the lesion on the ipsilateral side. We applied a combination treatment with acutely applied anti-Nogo-A antibody followed by delayed ChABC treatment starting at 3 weeks after injury, and rehabilitation starting at 4 weeks, to accommodate the requirement that anti-Nogo-A be applied acutely, and that rehabilitation be given after the cessation of anti-Nogo-A treatment. We found that single treatment with either anti-Nogo-A or ChABC, combined with rehabilitation, produced functional recovery of similar magnitude. The combination treatment, however, was more effective. Both single treatments produced increases in sprouting and axon regeneration, but the combination treatment produced greater increases. Anti-Nogo-A stimulated growth of a greater number of axons with a diameter of > 3 μm, whereas ChABC treatment stimulated increased growth of finer axons with varicosities. These results point to different functions of Nogo-A and chondroitin sulfate proteoglycans in axonal regeneration. The combination of anti-Nogo-A, ChABC and rehabilitation shows promise for enhancing functional recovery after SCI.

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Delayed rehabilitation with task-specific therapies improves forelimb function after a cervical spinal cord injury

Cited by 16 publications

References 64 publications

Quantifying changes following spinal cord injury with velocity dependent locomotor measures

Quantifying changes following spinal cord injury with velocity dependent locomotor measures

The Need for Speed in Rodent Locomotion Analyses

Combination treatment with anti‐Nogo‐A and chondroitinase ABC is more effective than single treatments at enhancing functional recovery after spinal cord injury

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